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Honeybees perform a number of sophisticated behaviours while foraging, during which they must learn and remember aspects of the flowers they visit to gather pollen.

Any disruption to this ability can have profound implications on their survival and that of the colony as a whole. Bees that cannot learn cannot find food and cannot return to their hives.

Combining two highly diverse resources from nature to create a biopesticide to protect honeybees is a milestone in scientific research.

“The main reasons for choosing this peptide (Hv1a) from the spider’s venom are that it is well studied and highly toxic to insects when injected,” said Martin Edwards, researcher in the university’s School of Biology.

“Previous research showed that the snowdrop lectin (GNA), following ingestion by insects, is transported across the gut and into the circulatory system: haemolymph, or their blood.

“As the venom peptide is only toxic when injected into insects — think of the spider capturing a prey and injecting its venom — we have fused the two proteins, hence Hv1a/GNA.

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“In that way, after the insect has ingested the fusion protein, GNA will transport the venom peptide from the insect’s gut to the haemolymph, and from there onto the targets in the central nervous system.”

Edwards is part of the research team supervised by professor Angharad Gatehouse, who in October was awarded the prestigious Certificate of Distinction for Outstanding Achievements by the Council of International Congresses of Entomology. It is the world’s top accolade in this field of science.

“Our findings suggest that Hv1a/GNA is unlikely to cause any detrimental effects on honeybees,” said Gatehouse. “Previous studies have already shown that it is safe for higher animals, which means it has real potential as a pesticide and offers us a safe alternative to some of those currently on the market.”

The honeybees were exposed to varying concentrations of the biopesticide over seven days, during which memory tests and behaviour observations were made. The oral pesticide ingested by the bees targeted their calcium channels.

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Co-researcher Erich Nakasu said the hv1a/GNA compound was carried to the brain of the honeybee but had no effect, which suggested that the selective spider venom toxin does not interact with the calcium channels in bees.

Many commercial insecticides act on specific insect receptors and ion channels, including voltage-gated sodium channels (VGSC) and voltage-gated calcium channels (VGCC). In honeybees, calcium channels are associated with learning, so pesticides cannot be allowed to interfere with their function.

Funnel-web spider venom is extremely toxic to primates, including humans, but it appears to be fairly harmless to many other species. Edwards said the venom showed no effect when injected into newborn mice or adult rabbits.

The fact that funnel-web spider venom does not cause toxicity in honeybees may be the beneficial result of the bee’s specific evolution.

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“Hymenoptera, including the honeybee (apis mellifera) and lepidoptera, including the targeted pests mamestra brassicae, may have evolved into individual species some 300 million years ago,” said Edwards.

“Insects typically have three genes encoding VGCCs, which are assumed to have diverse physiological roles. Therefore, as it is not yet known which version of the VGCC is targeted by the Hv1a/GNA fusion protein, one could conclude that overall, through evolution and divergence, the honeybee VGCCs are not compatible with the Hv1a (spider) toxin.

“These differences prevent the spider venom from interacting with these channels in bees. This is something that the group is currently investigating by studying the interaction between Hv1A/GNA and a honeybee VGCC using an in-vitro assay.”

The research has indicated that the biopesticide will not adversely affect plants.

As well, the team is working on the effects of the product on non-target species and have found no detrimental effects on beneficial insects such as predatory wasps.

Because neither of the compounds is toxic to vertebrates, they also believe the biopesticide to be safe for birds and many higher mammals.

Given that funnel-web spider venom is a rare commodity, commercial production of the biopesticide will require further biological development.

“The inventors of this technology, Durham University and the Food and Environment Research Agency, are working with industry to develop these biopesticides,” said Edwards.

“This fusion protein has been produced in a microbial expression system. The native toxin from the spider’s venom was not used and would be far too costly to do so. By using molecular biology techniques, a synthetic gene can be made that is a fusion between the gene encoding the Hv1a and the gene encoding the GNA.

This synthetic gene is introduced into a microbial expression system. A yeast makes many copies of the fusion protein, which can then be purified using traditional chromatography techniques. This does not mean that the biopesticide is genetically modified. Rather, the protein product is derived from a genetically modified organism.”

The project is part of the Insect Pollinators Initiative. Results of the study were published this summer in the journal Proceedings of the Royal Society B.